Matic left the London club after three and a half years to re-join former Chelsea manager Jose Mourinho at Old Trafford. He has played every minute in the league since, helping United to second place in the table, five points behind Manchester City.
Mourinho's capture of Matic is looking shrewder every week, prompting former United defender Phil Neville to say after Chelsea's 3-0 Champions League drubbing at AS Roma this week that selling the Serb was the main reason why Chelsea are struggling defensively.
His absence from Chelsea's midfield will be highlighted further should N'Golo Kante fail to recover from a hamstring injury.
The Frenchman is back in training but if he misses out against United, Chelsea will be without both members of the central midfield pairing that guided them to the title last season.
In their place, Cesc Fabregas and Tiemoue Bakayoko bring creative attacking qualities, but do not provide the extra cover Conte craves and United's pacy forwards could have the freedom to seriously threaten a fragile Chelsea defence that has conceded 10 league goals this season.
United's main striker Romelu Lukaku has gone six games without a goal, however, and Mourinho must decide whether to play Marcus Rashford and Anthony Martial together in the hope their raw speed and trickery can unsettle the Chelsea rearguard.
Earlier on Sunday, Manchester City bid to extend their record-equalling start to the campaign at home to Arsenal.
Pep Guardiola's side have looked invincible at times, winning their last eight league games by an aggregate score of 32-5.
However, City have only won one of their last nine matches against Arsenal and will be facing the Gunners after a testing away trip to Napoli, where they won 4-2 in the Champions League on Wednesday.
Chelsea and Manchester United, as well as Tottenham Hotspur who welcome Crystal Palace on Sunday, will be hoping Arsene Wenger's men can cause an upset at the Etihad and blow the title race wide open.
A win for Arsenal would also drag them back into contention. They lie fifth, nine points off the pace.
On Saturday, West Ham United host Liverpool and their under-pressure manager Slaven Bilic will be desperate to avoid the 4-0 mauling they suffered in last season's corresponding fixture.
(Reporting by Jack Tarrant; Editing by Christian Radnedge)
